Saturday, July 20, 2013

Tom Thum: The orchestra in my mouth

Tom Thum on the Web

Functional imaging (fMRI) of allodynia in CRPS

Brain cells are one thing an fMRI can't hone in on.         Purestock/Getty Images

This article dates from 2006 and yet I've not heard much mention of people with CRPS having access or using functional MRI to assess allodynia.  Most likely, it offers little real information that can be put to use within treatment, but may open doors and minds within the research community. Should it become part of the diagnostic protocol?  


Functional imaging of allodynia in complex regional pain syndrome

  1. Frank Birklein, MD, PhD
  1. Address correspondence and reprint requests to Dr. C. Maihöfner, Department of Neurology/Institute for Physiology and Experimental Pathophysiology, University of Erlangen–Nuremberg, Universitätsstrasse 17, D-91054 Erlangen, Germany;
  1. doi: 10.1212/01.wnl.0000200961.49114.39Neurologyvol. 66 no. 5 711-717

Objective: To investigate cerebral activations underlying touch-evoked pain (dynamic–mechanical allodynia) in patients with neuropathic pain.
Methods: fMRI was used in 12 patients with complex regional pain syndromes (CRPSs). Allodynia was elicited by gently brushing the affected CRPS hand. Elicited pain ratings were recorded online to obtain pain-weighted predictors. Both activations and deactivations of blood oxygenation level–dependent signals were investigated.
Results: Nonpainful stimulation on the nonaffected hand activated contralateral primary somatosensory cortex (S1), bilateral insula, and secondary somatosensory cortices (S2). In contrast, allodynia led to widespread cerebral activations, including contralateral S1 and motor cortex (M1), parietal association cortices (PA), bilateral S2, insula, frontal cortices, and both anterior and posterior parts of the cingulate cortex (aACC and pACC). Deactivations were detected in the visual, vestibular, and temporal cortices. When rating-weighted predictors were implemented, only few activations remained (S1/PA cortex, bilateral S2/insular cortices, pACC).
Conclusions: Allodynic stimulation recruits a complex cortical network. Activations include not only nociceptive but also motor and cognitive processing. Using a covariance approach (i.e., implementation of rating-weighted predictors) facilitates the detection of a neuronal matrix involved in the encoding of allodynia. The pattern of cortical deactivation during allodynia may hint at a shift of activation from tonically active sensory systems, like visual and vestibular cortices, into somatosensory-related brain areas.


There were, following publication, letters that pointed out both the study's strengths and one considerable weakness:

Functional imaging of allodynia in complex regional pain syndromeRon Kupers, PET Unit & Dept. Surgical Pathophysiology, Rigshospitalet
KF 3892, Blegdamsvej 9, 2100 Copenhagen, Denmark
Maihofner et al [1] describe fMRI data of allodynia in complex regional pain syndrome (CRPS). The authors are to be congratulated for a very carefully designed study. Of the 12 patients, 11 were suffering from pain and sensory abnormalities in the right hand. This homogeneity in the anatomical distribution of the pain complaints may explain why the authors obtained allodynia-induced activation of SI whereas other brain imaging studies failed/ [2]
Maihofner's study is also important because their pain-related activations are predominantly contralateral to the stimulated body area, conform with findings in acute, experimental pain studies. This contrasts with reports of bilateral responses in the pain matrix, often with a preponderence of responses in the hemisphere ipsilateral to stimulation. [2,3] Whereas these latter studies investigated neuropathic pain patients with minor [2] or major [3] lesions to the nervous system, Maihofner et al used CRPS-type I patients, a neuropathic pain condition characterized by an absence of lesion to the peripheral nervous system.
Taken together, this suggests that the ipsilateral activations are not driven by pain but may reflect central reorganization as a result of deafferentation. However, alternative interpretations cannot be excluded. For instance, the average duration of pain complaints in Maihofner's study is significantly shorter than in the two other reports (< 0.5 years compared to > 2 and > 5 years). [2,3]
Maihofner also reported a deactivation of the ipsilateral primary somatosensory cortex during non-painful brushing. They argue that this has never been reported in healthy subjects and and therefore they relate this finding to the chronic pain condition. We strongly disagree with this interpretation. Drevets et al [4] reported that anticipation of a painful stimulus causes a decrease in regional brain activity in parts of the somatosensory cortex ipsilateral to the location of the expected pain stimulus.
We showed that activity in ipsilateral SI in normal subjects decreases not only during the anticipation of a stimulus but also during actual somatosensory stimulation. [5] In another recent study in healthy volunteers, we found strong evidence for ipsilateral deactivations in SI (Figure 1). Taken together, the ipsilateral deactivation following allodynic brushing is unlikely to be linked to the chronic pain state. The most parsimonious explanation is that it reflects top-down anticipatory modulation elicited by attention to the expected stimulus.
1. Maihofner C, Handwerker HO, Birklein F. Functional imaging of allodynia in complex regional pain syndrome. Neurology 2006; 66: 711-7.
2. Witting N, Kupers RC, Svensson P, Jensen TS. A PET activation study of brush-evoked allodynia in patients with nerve injury pain. Pain 2006; 120: 145-54.
3. Peyron R, Schneider F, Faillenot I, Convers P, Barral FG, Garcia- Larrea L, Laurent B. An fMRI study of cortical representation of mechanical allodynia in patients with neuropathic pain. Neurology 2004; 63: 1838-46.
4. Drevets WC, Burton H, Videen TO, Snyder AZ, Simpson JR Jr, Raichle ME. Blood flow changes in human somatosensory cortex during anticipated stimulation. Nature 1995; 373: 249-52.
5. Kupers R, Svensson S, Jensen TS. Central representation of muscle pain and mechanical hyperesthesia in the orofacial region: a positron emission tomography study. Pain 2004, 108: 284-93.
Disclosure: The author reports no conflicts of interest.

The authors replied:

Christian Maihöfner, Department of Neurology, University of Erlangen Frank Birklein; Department of Neurology; University of Mainz; Germany
Schwabachanlage 6, 91054 Erlangen, Germany
We thank Dr. Kupers for his comments on our article. [1] The patients investigated in our study had no skin nerve lesions and had a moderate time in pain. Furthermore, we agree that one potential advantage of our study is that our patient group was homogenous with allodynia in one body region – hands. Dr. Kupers et al [2] and Dr. Peyron et al [3] investigated patients who complained of allodynia in very different body regions. In Peyron´s study [3], a significant proportion of patients even had pain from central origin (stroke). For stroke, significant central reorganization is obvious, but whether peripheral nerve lesions indeed affect encoding of allodynia in a way so that it occurs primarily in the ipsilateral brain hemisphere is speculative.
We also found bilateral responses after allodynic brushing in the medial affective pain system, as has been recently reported. [6] It seems reasonable that the major afferent pathways of touching, regardless of pain project in the lateral somatosensory discriminative system on the contralateral side as has been found in a previous PET- study of Dr. Witting and Dr. Kupers in experimental allodynia. [7] This confirms recent fMRI studies of our group. [8]
Regarding Dr. Kupers second point, we did not observe ipsilateral S1 deactivation after allodynic brushing. We observed ipsilateral S1 deactivation only after pleasant and non-painful brushing the healthy limb. We observed no ipsilateral deactivation during painful allodynia brushing when anticipation of the pain should be more intense than during pleasant touch. We continue to assume that ipsilateral S1 deactivation could be related to tonic activation of this brain region in unilateral chronic pain. Possibly tonic pre- activation also underlies the inconstant activation of the contralateral brain region as discussed above.
The increase of regional cerebral blood flow during brain activation (underlying BOLD effect and PET activation) will not be endless; there must be some asymptotic approach to a ceiling. We do agree that during somatosensory stimulation other leading sensory systems like visual or vestibular systems might become deactivated. This was one result of our study (see figure (E) F2). The underlying mechanisms and significance of BOLD deactivations are controversial. It is unclear what deactivations of the BOLD signal really mean (e.g. neuronal deactivation and or shift of attention). Further studies are needed to investigate the causes of ipsilateral S1 deactivation.

6. Schweinhardt P, Glynn C, Brooks J, McQuay H, Jack T, Chessell I et al. An fMRI study of cerebral processing of brush-evoked allodynia in neuropathic pain patients. Neuroimage 2006.
7. Witting N, Kupers RC, Svensson P, Arendt-Nielsen L, Gjedde A, Jensen TS. Experimental brush-evoked allodynia activates posterior parietal cortex. Neurology 2001;57:1817-1824.
8. Maihofner C, Schmelz M, Forster C, Neundorfer B, Handwerker HO. Neural activation during experimental allodynia: a functional magnetic resonance imaging study. Eur J Neurosci 2004;19:3211-3218.
Disclosure: The authors report no conflicts of interest.

© 2013 L. Ryan

Friday, July 19, 2013

To the Lincolnton Scoundrelettes

Ah, so you've taken to searching me out all over social media.  And following other people in cars. How... rude.  Ah, but when it comes to rudeness, I have no room to talk.  But then, this is my blog, a place protected by various things, including copyright law.  Reproductions are frowned upon.  Big old freaking frowns, too.

But then, I do have manners.
I wasn't raised in no dang barn.

Enjoy yourselves, make yourselves at home.  We've a whole empty outbuilding that can be fixed up for you, your children, your pets, lovers, friends, fiancés, and any stray relatives who'd love to tag along. It is just beyond the Animal Husbandry Barn Yard, at a suitable distance from the Insemination Gazebo, and far enough from our wing of Marlinspike Hall that you shall not feel spied upon.

One thing you should remember about this blog:  it's my place to vent, say what I please (but not necessarily what I believe), and to people who are my friends, be they of the Hergé sort or just soft-spoken Buddhist anarchists who have decided to live in a haus-boat that continually circles the moat.  It's also a place for people with CRPS to share research and clinical trial news, and a place for them to relax, to go aside and rest awhile.

I say some mean things here about you, about Mom.  I say a lot of nice things about you here, too, and about Mom.  I say them as I say them.  I say them as I feel them.  I say them based on things I know and you don't.  Sometimes I base them on misinformation that is fed to me.

I would appreciate being able to telephone the Mother-Unit without interference or the necessity of aid from sweet third parties.  But it's no big deal.  I truly hate the telephone.  There's not much to say on my end.  One day is remarkably like the other.  There's no point to your interference.  Who and what you are is known.  Most of what you've done is known, or guessed at.  And no one much cares.

In a random poll taken in the neighborhood, a hefty 99% of the polled say it's time for you to grow up.  So you go do that.

I'll stay here and make sure the ticking in your mattresses is the absolute freshest, that there are daisies, lilies, and tulips (for Lale) in cut-glass vases throughout the charmingly converted building come to be known simply as "The Turkey Baster." We need to rename it but that kind of thing just is not a priority.  If I have time to do some growing up, it will have to be between re-sodding our Wimbledon Replica Courts and baking a thousand caramelized onion with tomato jam tarts for the local Woe-Is-Me Chapter Fundraiser.

Be careful as you stroll about elle est belle la seine la seine elle est belle.  Tante Louise, the local constabulary and gossip comptroller, patrols various posts and hallways.  She doesn't take kindly to litter, prevarication, violence, manipulation, or vandalism (which she defines in a most... original way).

Also take care that you do not in any way meander off the beaten path into the domains of my Brother-Units.  I consider myself their Gate Keeper, and you know what that means.  Anything goes and no one crosses that line.

There's no reason on God's formerly green Earth that relationships cannot be mended.  There is one criterion that can't be avoided, however, and, well, I would hope that is obvious by now.

You are worthy people, children of the aforementioned God, guests on His formerly green Earth. Be generous.  Be real.  Be compassionate.

I will try to learn to do the same.  My learning curve is not the greatest.  But I won't give up trying. I promise.  So let's not give up on one another, no matter how angry we feel.

You're surrounded by some good people -- Betty, Mac, Benita -- and you've access to many more. Listen to older, wiser voices.  There is nothing new under the sun.  This drama?  It's happening all over God's formerly green Earth, and began with the First Family -- by which I do not mean President Obama and his good kin.

This above all else, my half-siblings:  the next generation, those kids you are rasining?  Spare them the mistakes that we have made.  Expose them to new things, allow them to explore, allow them to disagree, give them some space.  Get them help if they need it.  Love them in such a way that they don't grow up confused about love or where to find it.  Let them know that their hearts are safe in your homes, and that's where their hearts will be. You've got real treasures in your care -- they are wonderful children!

Transcript of President Obama's Comments on Race and the Zimmerman Trial

Welcome back, Mr. President!

The reason I actually wanted to come out today is not to take questions, but to speak to an issue that obviously has gotten a lot of attention over the course of the last week, the issue of the Trayvon Martin ruling. I gave an -- a preliminary statement right after the ruling on Sunday, but watching the debate over the course of the last week I thought it might be useful for me to expand on my thoughts a little bit.

First of all, you know, I -- I want to make sure that, once again, I send my thoughts and prayers, as well as Michelle’s, to the family of Trayvon Martin, and to remark on the incredible grace and dignity with which they’ve dealt with the entire situation. I can only imagine what they’re going through, and it’s -- it’s remarkable how they’ve handled it.

The second thing I want to say is to reiterate what I said on Sunday, which is there are going to be a lot of arguments about the legal -- legal issues in the case. I’ll let all the legal analysts and talking heads address those issues.

The judge conducted the trial in a professional manner. The prosecution and the defense made their arguments. The juries were properly instructed that in a -- in a case such as this, reasonable doubt was relevant, and they rendered a verdict. And once the jury’s spoken, that’s how our system works.

But I did want to just talk a little bit about context and how people have responded to it and how people are feeling. You know, when Trayvon Martin was first shot, I said that this could have been my son. Another way of saying that is Trayvon Martin could have been me 35 years ago. And when you think about why, in the African- American community at least, there’s a lot of pain around what happened here, I think it’s important to recognize that the African- American community is looking at this issue through a set of experiences and a history that -- that doesn’t go away.

There are very few African-American men in this country who haven’t had the experience of being followed when they were shopping in a department store. That includes me.

And there are very few African-American men who haven’t had the experience of walking across the street and hearing the locks click on the doors of cars. That happens to me, at least before I was a senator. There are very few African-Americans who haven’t had the experience of getting on an elevator and a woman clutching her purse nervously and holding her breath until she had a chance to get off. That happens often.

And you know, I don’t want to exaggerate this, but those sets of experiences inform how the African-American community interprets what happened one night in Florida. And it’s inescapable for people to bring those experiences to bear.

The African-American community is also knowledgeable that there is a history of racial disparities in the application of our criminal laws, everything from the death penalty to enforcement of our drug laws. And that ends up having an impact in terms of how people interpret the case.

Now, this isn’t to say that the African-American community is naive about the fact that African-American young men are disproportionately involved in the criminal justice system, that they are disproportionately both victims and perpetrators of violence. It’s not to make excuses for that fact, although black folks do interpret the reasons for that in a historical context.

We understand that some of the violence that takes place in poor black neighborhoods around the country is born out of a very violent past in this country, and that the poverty and dysfunction that we see in those communities can be traced to a very difficult history.

And so the fact that sometimes that’s unacknowledged adds to the frustration. And the fact that a lot of African-American boys are painted with a broad brush and the excuse is given, well, there are these statistics out there that show that African-American boys are more violent -- using that as an excuse to then see sons treated differently causes pain.

I think the African-American community is also not naive in understanding that statistically somebody like Trayvon Martin was probably statistically more likely to be shot by a peer than he was by somebody else.

So -- so folks understand the challenges that exist for African- American boys, but they get frustrated, I think, if they feel that there’s no context for it or -- and that context is being denied. And -- and that all contributes, I think, to a sense that if a white male teen was involved in the same kind of scenario, that, from top to bottom, both the outcome and the aftermath might have been different.

Now, the question for me at least, and I think, for a lot of folks is, where do we take this? How do we learn some lessons from this and move in a positive direction? You know, I think it’s understandable that there have been demonstrations and vigils and protests, and some of that stuff is just going to have to work its way through as long as it remains nonviolent. If I see any violence, then I will remind folks that that dishonors what happened to Trayvon Martin and his family.

But beyond protests or vigils, the question is, are there some concrete things that we might be able to do? I know that Eric Holder is reviewing what happened down there, but I think it’s important for people to have some clear expectations here. Traditionally, these are issues of state and local government -- the criminal code. And law enforcement has traditionally done it at the state and local levels, not at the federal levels.

That doesn’t mean, though, that as a nation, we can’t do some things that I think would be productive. So let me just give a couple of specifics that I’m still bouncing around with my staff so we’re not rolling out some five-point plan, but some areas where I think all of us could potentially focus.

Number one, precisely because law enforcement is often determined at the state and local level, I think it’d be productive for the Justice Department -- governors, mayors to work with law enforcement about training at the state and local levels in order to reduce the kind of mistrust in the system that sometimes currently exists.

You know, when I was in Illinois I passed racial profiling legislation. And it actually did just two simple things. One, it collected data on traffic stops and the race of the person who was stopped. But the other thing was it resourced us training police departments across the state on how to think about potential racial bias and ways to further professionalize what they were doing.

And initially, the police departments across the state were resistant, but actually they came to recognize that if it was done in a fair, straightforward way, that it would allow them to do their jobs better and communities would have more confidence in them and in turn be more helpful in applying the law. And obviously law enforcement’s got a very tough job.

So that’s one area where I think there are a lot of resources and best practices that could be brought bear if state and local governments are receptive. And I think a lot of them would be. And -- and let’s figure out other ways for us to push out that kind of training.

Along the same lines, I think it would be useful for us to examine some state and local laws to see if it -- if they are designed in such a way that they may encourage the kinds of altercations and confrontations and tragedies that we saw in the Florida case, rather than defuse potential altercations.

I know that there’s been commentary about the fact that the stand your ground laws in Florida were not used as a defense in the case.

On the other hand, if we’re sending a message as a society in our communities that someone who is armed potentially has the right to use those firearms even if there’s a way for them to exit from a situation, is that really going to be contributing to the kind of peace and security and order that we’d like to see?

And for those who resist that idea that we should think about something like these “stand your ground” laws, I just ask people to consider if Trayvon Martin was of age and armed, could he have stood his ground on that sidewalk? And do we actually think that he would have been justified in shooting Mr. Zimmerman, who had followed him in a car, because he felt threatened?

And if the answer to that question is at least ambiguous, it seems to me that we might want to examine those kinds of laws.

Number three -- and this is a long-term project: We need to spend some time in thinking about how do we bolster and reinforce our African-American boys? And this is something that Michelle and I talk a lot about. There are a lot of kids out there who need help who are getting a lot of negative reinforcement. And is there more that we can do to give them the sense that their country cares about them and values them and is willing to invest in them?

You know, I’m not naive about the prospects of some brand-new federal program.

I’m not sure that that’s what we’re talking about here. But I do recognize that as president, I’ve got some convening power.

And there are a lot of good programs that are being done across the country on this front. And for us to be able to gather together business leaders and local elected officials and clergy and celebrities and athletes and figure out how are we doing a better job helping young African-American men feel that they’re a full part of this society and that -- and that they’ve got pathways and avenues to succeed -- you know, I think that would be a pretty good outcome from what was obviously a tragic situation. And we’re going to spend some time working on that and thinking about that.

And then finally, I think it’s going to be important for all of us to do some soul-searching. You know, there have been talk about should we convene a conversation on race. I haven’t seen that be particularly productive when politicians try to organize conversations. They end up being stilted and politicized, and folks are locked into the positions they already have.

On the other hand, in families and churches and workplaces, there’s a possibility that people are a little bit more honest, and at least you ask yourself your own questions about, am I wringing as much bias out of myself as I can; am I judging people, as much as I can, based on not the color of their skin but the content of their character? That would, I think, be an appropriate exercise in the wake of this tragedy.

And let me just leave you with -- with a final thought, that as difficult and challenging as this whole episode has been for a lot of people, I don’t want us to lose sight that things are getting better. Each successive generation seems to be making progress in changing attitudes when it comes to race. I doesn’t mean that we’re in a postracial society. It doesn’t mean that racism is eliminated. But you know, when I talk to Malia and Sasha and I listen to their friends and I see them interact, they’re better than we are. They’re better than we were on these issues. And that’s true in every community that I’ve visited all across the country.

And so, you know, we have to be vigilant and we have to work on these issues, and those of us in authority should be doing everything we can to encourage the better angels of our nature as opposed to using these episodes to heighten divisions. But we should also have confidence that kids these days I think have more sense than we did back then, and certainly more than our parents did or our grandparents did, and that along this long, difficult journey, you know, we’re becoming a more perfect union -- not a perfect union, but a more perfect union.

All right? Thank you, guys.

Dobby and Buddy: A Portrait of Guilt

 photo 6eacc07b-98f0-401d-aa9c-94217861a6c6.jpg

Tuesday, July 16, 2013

Silverman on Scott Walker

From Daily Kos

"This is Trayvon Martin's body": Get Angry.

This is Trayvon Martin's body. These are the last skinny jeans he wore, cuffed once at the bottoms. These are his stylish kicks, his sockless ankles. There are Trayvon's taut neck, his slack jaw, his open eyes.

This is what happens. Not just when we input "black" and "teen" and "hoodie" and "night" into our onboard computers and output "DANGER," but also when we find the aftermath Newsworthy, and must consume it voraciously from start to finish, but insist that we cannot stomach seeing the bones and gristle on our plates.

-- ADAM WEINSTEIN, from Gawker